Medicine (RMH) - Research Publications
Permanent URI for this collection
Search Results
1 - 10 of 21
-
ItemNo Preview AvailableSustaining a New Model of Acute Stroke Care: A Mixed- Method Process Evaluation of the Melbourne Mobile Stroke Unit(KERMAN UNIV MEDICAL SCIENCES, 2023-01)BACKGROUND: Internationally, Mobile Stroke Unit (MSU) ambulances have changed pre-hospital acute stroke care delivery. MSU clinical and cost-effectiveness studies are emerging, but little is known about important factors for achieving sustainability of this innovative model of care. METHODS: Mixed-methods study from the Melbourne MSU (operational since November 2017) process evaluation. Participant purposive sampling included clinical, operational and executive/management representatives from Ambulance Victoria (AV) (emergency medical service provider), the MSU clinical team, and receiving hospitals. Sustainability was defined as ongoing MSU operations, including MSU workforce and future model considerations. Theoretically-based on-line survey with Unified Theory of Acceptance and Use of Technology (UTAUT), Self Determination Theory (SDT, Intrinsic Motivation), and open-text questions targeting barriers and benefits was administered (June-September 2019). Individual/group interviews were conducted, eliciting improvement suggestions and requirements for ongoing use. Descriptive and regression analyses (quantitative data) and directed content and thematic analysis (open text and interview data) were conducted. RESULTS: There were 135 surveys completed. Identifying that the MSU was beneficial to daily work (β=0.61), not experiencing pressure/tension about working on the MSU (β=0.17) and thinking they did well working within the team model (β=0.17) were significantly associated with wanting to continue working within the MSU model [R2=0.76; F(15, 60)=12.76, P<.001]. Experiences varied between those on the MSU team and those working with the MSU. Advantages were identified for patients (better, faster care) and clinicians (interdisciplinary learning). Disadvantages included challenges integrating into established systems, and establishing working relationships. Themes identified from 35 interviews were MSU team composition, MSU vehicle design and layout, personnel recruitment and rostering, communication improvements between organisations, telemedicine options, MSU operations and dispatch specificity. CONCLUSION: Important factors affecting the sustainability of the MSU model of stroke care emerged. A cohesive team approach, with identifiable benefits and good communication between participating organisations is important for clinical and operational sustainability.
-
ItemNo Preview AvailablePrevalence and Significance of Impaired Microvascular Tissue Reperfusion Despite Macrovascular Angiographic Reperfusion (No-Reflow)(LIPPINCOTT WILLIAMS & WILKINS, 2022-02-22)BACKGROUND AND OBJECTIVES: The relevance of impaired microvascular tissue-level reperfusion despite complete upstream macrovascular angiographic reperfusion (no-reflow) in human stroke remains controversial. We investigated the prevalence and clinical-radiologic features of this phenomenon and its associations with outcomes in 3 international randomized controlled thrombectomy trials with prespecified follow-up perfusion imaging. METHODS: In a pooled analysis of the Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA; ClinicalTrials.gov NCT01492725), Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK; NCT02388061), and Determining the Optimal Dose of Tenecteplase Before Endovascular Therapy for Ischaemic Stroke (EXTEND-IA TNK Part 2; NCT03340493) trials, patients undergoing thrombectomy with final angiographic expanded Treatment in Cerebral Infarction score of 2c to 3 score for anterior circulation large vessel occlusion and 24-hour follow-up CT or MRI perfusion imaging were included. No-reflow was defined as regions of visually demonstrable persistent hypoperfusion on relative cerebral blood volume or flow maps within the infarct and verified quantitatively by >15% asymmetry compared to a mirror homolog in the absence of carotid stenosis or reocclusion. RESULTS: Regions of no-reflow were identified in 33 of 130 patients (25.3%), encompassed a median of 60.2% (interquartile range 47.8%-70.7%) of the infarct volume, and involved both subcortical (n = 26 of 33, 78.8%) and cortical (n = 10 of 33, 30.3%) regions. Patients with no-reflow had a median 25.2% (interquartile range 16.4%-32.2%, p < 0.00001) relative cerebral blood volume interside reduction and 19.1% (interquartile range 3.9%-28.3%, p = 0.00011) relative cerebral blood flow reduction but similar mean transit time (median -3.3%, interquartile range -11.9% to 24.4%, p = 0.24) within the infarcted region. Baseline characteristics were similar between patients with and those without no-reflow. The presence of no-reflow was associated with hemorrhagic transformation (adjusted odds ratio [aOR] 1.79, 95% confidence interval [CI] 2.32-15.57, p = 0.0002), greater infarct growth (β = 11.00, 95% CI 5.22-16.78, p = 0.00027), reduced NIH Stroke Scale score improvement at 24 hours (β = -4.06, 95% CI 6.78-1.34, p = 0.004) and being dependent or dead at 90 days as assessed by the modified Rankin Scale (aOR 3.72, 95% CI 1.35-10.20, p = 0.011) in multivariable analysis. DISCUSSION: Cerebral no-reflow in humans is common, can be detected by its characteristic perfusion imaging profile using readily available sequences in the clinical setting, and is associated with posttreatment complications and being dependent or dead. Further studies evaluating the role of no-reflow in secondary injury after angiographic reperfusion are warranted. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that cerebral no-reflow on CT/MRI perfusion imaging at 24 hours is associated with posttreatment complications and poor 3-month functional outcome.
-
ItemNo Preview AvailableEndovascular Thrombectomy Versus Medical Management in Isolated M2 Occlusions: Pooled Patient-Level Analysis from the EXTEND-IA Trials, INSPIRE, and SELECT Studies(WILEY, 2022-05)OBJECTIVE: The objective of this study was to evaluate functional and safety outcomes of endovascular thrombectomy (EVT) versus medical management (MM) in patients with M2 occlusion and examine their association with perfusion imaging mismatch and stroke severity. METHODS: In a pooled, patient-level analysis of 3 randomized controlled trials (EXTEND-IA, EXTEND-and IA-TNK parts 1 and 2) and 2 prospective nonrandomized studies (INSPIRE and SELECT), we evaluated EVT association with 90-day functional independence (modified Rankin Scale [mRS] = 0-2) in isolated M2 occlusions as compared to medical management overall and in subgroups by mismatch profile status and stroke severity. RESULTS: We included 517 patients (EVT = 195 and MM = 322), baseline median (interquartile range [IQR]) National Institutes of Health Stroke Scale (NIHSS) was 13 (8-19) in EVT versus 10 (6-15) in MM, p < 0.001. Pretreatment ischemic core did not differ (EVT = 10 [0-24] ml vs MM = 9 [3-21] ml, p = 0.59). Compared to MM, EVT was more frequently associated with functional independence (68.3 vs 61.6%, adjusted odds ratio [aOR] = 2.42, 95% confidence interval [CI] = 1.25-4.67, p = 0.008, inverse probability of treatment weights [IPTW]-OR = 1.75, 95% CI = 1.00-3.75, p = 0.05) with a shift toward better mRS outcomes (adjusted cOR = 2.02, 95% CI:1.23-3.29, p = 0.005), and lower mortality (5 vs 10%, aOR = 0.32, 95% CI = 0.12-0.87, p = 0.025). EVT was associated with higher functional independence in patients with a perfusion mismatch profile (EVT = 70.7% vs MM = 61.3%, aOR = 2.29, 95% CI = 1.09-4.79, p = 0.029, IPTW-OR = 2.02, 1.08-3.78, p = 0.029), whereas no difference was found in those without mismatch (EVT = 43.8% vs MM = 62.7%, p = 0.17, IPTW-OR: 0.71, 95% CI = 0.18-2.78, p = 0.62). Functional independence was more frequent with EVT in patients with moderate or severe strokes, as defined by baseline NIHSS above any thresholds from 6 to 10, whereas there was no difference between groups with milder strokes below these thresholds. INTERPRETATION: In patients with M2 occlusion, EVT was associated with improved clinical outcomes when compared to MM. This association was primarily observed in patients with a mismatch profile and those with higher stroke severity. ANN NEUROL 2022;91:629-639.
-
ItemNo Preview AvailableHealthy Life-Year Costs of Treatment Speed From Arrival to Endovascular Thrombectomy in Patients With Ischemic Stroke A Meta-analysis of Individual Patient Data From 7 Randomized Clinical Trials(AMER MEDICAL ASSOC, 2021-06)IMPORTANCE: The benefits of endovascular thrombectomy (EVT) are time dependent. Prior studies may have underestimated the time-benefit association because time of onset is imprecisely known. OBJECTIVE: To assess the lifetime outcomes associated with speed of endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion (LVO). DATA SOURCES: PubMed was searched for randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time, and for which a peer-reviewed, complete primary results article was published by August 1, 2020. STUDY SELECTION: All randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time were included. DATA EXTRACTION/SYNTHESIS: Patient-level data regarding presenting clinical and imaging features and functional outcomes were pooled from the 7 retrieved randomized clinical trials of stent retriever thrombectomy devices (entirely or predominantly) vs medical therapy. All 7 identified trials published in a peer-reviewed journal (by August 1, 2020) contributed data. Detailed time metrics were collected including last known well-to-door (LKWTD) time; last known well/onset-to-puncture (LKWTP) time; last known well-to-reperfusion (LKWR) time; door-to-puncture (DTP) time; and door-to-reperfusion (DTR) time. MAIN OUTCOMES AND MEASURES: Change in healthy life-years measured as disability-adjusted life-years (DALYs). DALYs were calculated as the sum of years of life lost (YLL) owing to premature mortality and years of healthy life lost because of disability (YLD). Disability weights were assigned using the utility-weighted modified Rankin Scale. Age-specific life expectancies without stroke were calculated from 2017 US National Vital Statistics. RESULTS: Among the 781 EVT-treated patients, 406 (52.0%) were early-treated (LKWTP ≤4 hours) and 375 (48.0%) were late-treated (LKWTP >4-12 hours). In early-treated patients, LKWTD was 188 minutes (interquartile range, 151.3-214.8 minutes) and DTP 105 minutes (interquartile range, 76-135 minutes). Among the 298 of 380 (78.4%) patients with substantial reperfusion, median DTR time was 145.0 minutes (interquartile range, 111.5-185.5 minutes). Care process delays were associated with worse clinical outcomes in LKW-to-intervention intervals in early-treated patients and in door-to-intervention intervals in early-treated and late-treated patients, and not associated with LKWTD intervals, eg, in early-treated patients, for each 10-minute delay, healthy life-years lost were DTP 1.8 months vs LKWTD 0.0 months; P < .001. Considering granular time increments, the amount of healthy life-time lost associated with each 1 second of delay was DTP 2.2 hours and DTR 2.4 hours. CONCLUSIONS AND RELEVANCE: In this study, care delays were associated with loss of healthy life-years in patients with acute ischemic stroke treated with EVT, particularly in the postarrival time period. The finding that every 1 second of delay was associated with loss of 2.2 hours of healthy life may encourage continuous quality improvement in door-to-treatment times.
-
ItemCost-Effectiveness of Monitoring Patients Post-Stroke With Mobile ECG During the Hospital Stay(WILEY, 2022-04-19)Background The effectiveness of a nurse-led in-hospital monitoring protocol with mobile ECG (iECG) was investigated for detecting atrial fibrillation in patients post-ischemic stroke or post-transient ischemic attack. The study aimed to assess the cost-effectiveness of using iECG during the initial hospital stay compared with standard 24-hour Holter monitoring. Methods and Results A Markov microsimulation model was constructed to simulate the lifetime health outcomes and costs. The rate of atrial fibrillation detection in iECG and Holter monitoring during the in-hospital phase and characteristics of modeled population (ie, age, sex, CHA2DS2-VASc) were informed by patient-level data. Costs related to recurrent stroke, stroke management, medications (new oral anticoagulants), and rehabilitation were included. The cost-effectiveness analysis outcome was calculated as an incremental cost per quality-adjusted life-year gained. As results, monitoring patients with iECG post-stroke during the index hospitalization was associated with marginally higher costs (A$31 196) and greater benefits (6.70 quality-adjusted life-years) compared with 24-hour Holter surveillance (A$31 095 and 6.66 quality-adjusted life-years) over a 20-year time horizon, with an incremental cost-effectiveness ratio of $3013/ quality-adjusted life-years. Monitoring patients with iECG also contributed to lower recurrence of stroke and stroke-related deaths (140 recurrent strokes and 20 deaths avoided per 10 000 patients). The probabilistic sensitivity analyses suggested iECG is highly likely to be a cost-effective intervention (100% probability). Conclusions A nurse-led iECG monitoring protocol during the acute hospital stay was found to improve the rate of atrial fibrillation detection and contributed to slightly increased costs and improved health outcomes. Using iECG to monitor patients post-stroke during initial hospitalization is recommended to complement routine care.
-
ItemTenecteplase versus Alteplase for Stroke Thrombolysis Evaluation Trial in the Ambulance (Mobile Stroke Unit-TASTE-A): protocol for a prospective randomised, open-label, blinded endpoint, phase II superiority trial of tenecteplase versus alteplase for ischaemic stroke patients presenting within 4.5 hours of symptom onset to the mobile stroke unit(BMJ PUBLISHING GROUP, 2022-04)INTRODUCTION: Mobile stroke units (MSUs) equipped with a CT scanner are increasingly being used to assess and treat stroke patients' prehospital with thrombolysis and transfer them to the most appropriate hospital for ongoing stroke care and thrombectomy when indicated. The effect of MSUs in both reducing the time to reperfusion treatment and improving patient outcomes is now established. There is now an opportunity to improve the efficacy of treatment provided by the MSU. Tenecteplase is a potent plasminogen activator, which may have benefits over the standard of care stroke lytic alteplase. Specifically, in the MSU environment tenecteplase presents practical benefits since it is given as a single bolus and does not require an infusion over an hour like alteplase. OBJECTIVE: In this trial, we seek to investigate if tenecteplase, given to patients with acute ischaemic stroke as diagnosed on the MSU, improves the rate of early reperfusion. METHODS AND ANALYSIS: TASTE-A is a prospective, randomised, open-label, blinded endpoint (PROBE) phase II trial of patients who had an ischaemic stroke assessed in an MSU within 4.5 hours of symptom onset. The primary endpoint is early reperfusion measured by the post-lysis volume of the CT perfusion lesion performed immediately after hospital arrival. ETHICS AND DISSEMINATION: The study was approved by the Royal Melbourne Hospital Human Ethics committee. The findings will be published in peer-reviewed journals, presented at academic conferences and disseminated among consumer and healthcare professional audiences. TRIAL REGISTRATION NUMBER: NCT04071613.
-
ItemDIRECT-SAFE: A Randomized Controlled Trial of DIRECT Endovascular Clot Retrieval versus Standard Bridging Therapy(KOREAN STROKE SOC, 2022-01)BACKGROUND AND PURPOSE: The benefit regarding co-treatment with intravenous (IV) thrombolysis before mechanical thrombectomy in acute ischemic stroke with large vessel occlusion remains unclear. To test the hypothesis that clinical outcome of ischemic stroke patients with intracranial internal carotid artery, middle cerebral artery or basilar artery occlusion treated with direct endovascular thrombectomy within 4.5 hours will be non-inferior compared with that of standard bridging IV thrombolysis followed by endovascular thrombectomy. METHODS: To randomize 780 patients 1:1 to direct thrombectomy or bridging IV thrombolysis with thrombectomy. An international-multicenter prospective randomized open label blinded endpoint trial (PROBE) (ClincalTrials.gov identifier: NCT03494920). RESULTS: Primary endpoint is functional independence defined as modified Rankin Scale (mRS) 0-2 or return to baseline at 90 days. Secondary end points include ordinal mRS analysis, good angiographic reperfusion (modified Thrombolysis in Cerebral Infarction score [mTICI] 2b-3), safety endpoints include symptomatic intracerebral hemorrhage and death. CONCLUSION: s DIRECT-SAFE will provide unique information regarding the impact of direct thrombectomy in patients with large vessel occlusion, including patients with basilar artery occlusion, with comparison across different ethnic groups.
-
ItemTranexamic acid for intracerebral haemorrhage within 2 hours of onset: protocol of a phase II randomised placebo-controlled double-blind multicentre trial(BMJ PUBLISHING GROUP, 2022-04)RATIONALE: Haematoma growth is common early after intracerebral haemorrhage (ICH), and is a key determinant of outcome. Tranexamic acid, a widely available antifibrinolytic agent with an excellent safety profile, may reduce haematoma growth. METHODS AND DESIGN: Stopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units (STOP-MSU) is a phase II double-blind, randomised, placebo-controlled, multicentre, international investigator-led clinical trial, conducted within the estimand statistical framework. HYPOTHESIS: In patients with spontaneous ICH, treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo. SAMPLE SIZE ESTIMATES: A sample size of 180 patients (90 in each arm) would be required to detect an absolute difference in the primary outcome of 20% (placebo 39% vs treatment 19%) under a two-tailed significance level of 0.05. An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients. INTERVENTION: Participants will receive 1 g intravenous tranexamic acid over 10 min, followed by 1 g intravenous tranexamic acid over 8 hours; or matching placebo. PRIMARY EFFICACY MEASURE: The primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours, defined as either ≥33% relative increase or ≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan. DISCUSSION: We describe the rationale and protocol of STOP-MSU, a phase II trial of tranexamic acid in patients with ICH within 2 hours from onset, based in participating mobile stroke units and emergency departments.
-
ItemDoes variability in automated perfusion software outputs for acute ischemic stroke matter? Reanalysis of EXTEND perfusion imaging(WILEY, 2022-01)AIMS: We reprocessed the Extending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND) perfusion imaging with a different automated software with the aim of comparing mismatch eligibility and outcomes. METHODS: EXTEND baseline perfusion imaging data were reprocessed using autoMIStar software to identify patients who were eligible based on the same target mismatch criteria as per the original trial. RESULTS: From the 225 patients fulfilling RAPID-based mismatch criteria randomized in the EXTEND study, 196 (87%) patients met the revised mismatch criteria. Most common reasons for not meeting revised criteria were core >70 ml (n = 9), and no perfusion lesion/lack of penumbral tissue (n = 20). The revised perfusion lesion volumes were significantly smaller compared to the original RAPID volumes (median 68 ml IQR 34-102 ml vs. 42 ml 16-92 ml, p = 0.036). Of the patients who met the revised mismatch criteria, 40% receiving alteplase had modified Rankin Scale (mRS) 0-1 at 3-month compared to 28% with placebo (Adjusted Odds Ratio (OR) = 2.23, CI 1.08-4.58, p = 0.028). In contrast, in the original mismatch cohort, 35% receiving alteplase had mRS 0-1 at 3-month compared to 30% with placebo (adjusted OR = 1.88, p = 0.056). CONCLUSIONS: These data reinforce the benefit of alteplase in the later time window, and suggest that differences in automated perfusion imaging software outputs may be clinically relevant.
-
ItemAdverse Outcomes Associated With Higher Mean Blood Pressure and Greater Blood Pressure Variability Immediately After Successful Embolectomy in Those With Acute Ischemic Stroke, and the Influence of Pretreatment Collateral Circulation Status(WILEY, 2021-03-02)Background To investigate whether collateral status could modify the associations between post-thrombectomy blood pressure (BP) measures and outcomes. Methods and Results Patients with anterior-circulation large-vessel-occlusion successfully recanalized in a multicenter endovascular thrombectomy registry were enrolled. Pretreatment collateral status was graded and dichotomized (good/poor) in angiography. Maximum, minimum, and mean systolic BP (SBP) and BP variability (assessed by the SD, coefficient of variation) during the initial 24 hours after endovascular thrombectomy were obtained. The primary outcome was unfavorable 90-day outcome (modified Rankin Scale score 3-6). Secondary outcomes included symptomatic intracranial hemorrhage and 90-day mortality. Adjusted odds ratios (aOR) of BP parameters over the outcomes were obtained in all patients and in patients with good/poor collaterals. Among 596 patients (mean age 66 years; 59.9% males), 302 (50.7%) patients had unfavorable 90-day outcome. In multivariable analyses, higher mean SBP (aOR, 1.59 per 10 mm Hg increment; 95% CI, 1.26-2.02; P<0.001), mean SBP >140 mm Hg (versus ≤120 mm Hg; aOR, 4.27; 95% CI, 1.66-10.97; P=0.002), and higher SBP SD (aOR, 1.08 per 1-SD increment; 95% CI, 1.01-1.16; P=0.02) were respectively associated with unfavorable 90-day outcome in patients with poor collateral but not in those with good collateral. A marginal interaction between SBP coefficient of variation tertiles and collaterals on 90-day functional outcome (P for interaction, 0.09) was observed. A significant interaction between SBP coefficient of variation tertiles and collaterals on 90-day mortality (P for interaction, 0.03) was observed. Conclusions Higher postprocedural BP is associated with 90-day unfavorable outcomes after successful endovascular thrombectomy in patients with poor collateral. Registration URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1900022154.